The multiplicity of cytochromes P-450 is being studied with monoclonal antibodies (MAbs) to 3-methylcholanthrene (MC)- and phenobarbital (PB)-induced rat liver cytochrome P-450. These MAbs directly bind both the corresponding microsomes and purified cytochrome P-450. A semiquantitative, direct radioimmunoassay (RIA) has been developed to measure cytochrome P-450 in the microsomes from various tissues in animals that are untreated, or treated with MC or PB. The amounts of cytochrome P-450 in different tissues and species, including human samples such as placentas and lymphocytes, are also being examined by competitive RIA; individual differences have been observed by this method, which is more reliable than measurements of enzyme activity. RIAs with multiple MAbs have also been used to define the epitopic content of cytochromes P-450, with the goal of classifying various tissues with respect to MAb-specific cytochromes. These analyses provide an approach to the study of cytochrome P-450 multiplicity that is complementary to enzymatic and structural studies. Development of rapid, efficient RIA methods will aid in the establishment of a detailed atlas of epitope-defined cytochromes P-450 present in different tissues, species, and strains of laboratory animals as well as humans, and will aid in understanding the diversity of the cytochromes P-450 and their role in individual susceptibility to carcinogenesis.